The objective of this study is to determine whether endogenous growth hormone (GH) regulates carbohydrate metabolism in normal animals by modulating sensitivity to insulin and by direct effects on peripheral carbohydrate utilization. To pinpoint the specific contribution of GH to carbohydrate homeostasis in animals with intact endocrine function, antibodies to rat GH (ArGH) are administered to normal rats to neutralize their endogenous GH. The acute metabolic consequences of isolated GH deficiency are being followed. The effectiveness of ArGH treatment in neutralizing the activity of endogenous GH is tested biologically and immunologically. Representative aspects of carbohydrate, lipid and protein metabolism are measured on serial plasma samples obtained via indwelling cannulas, and in tissues taken from the animals at the end of treatment. Glucose and insulin tolerance tests are also performed. Since compensatory changes can occur in normal rats treated with ArGH, glucose utilization and insulin sensitivity is also tested directly in vitro. After 3-hour ArGH treatment, enhanced sensitivity to insulin is evident in isolated adipocytes, and the binding of insulin is being explored as a potential mechanism. Insulin sensitivity is also being examined in muscle. Rapid metabolic changes accompanying ArGH treatment provide information on the role of endogenous GH in the moment to moment regulation of carbohydrate metabolism. This animal model will be used to identify possible mediators of the actions of GH, and to study relationships between the effects of GH and glucocorticoids on insulin sensitivity and glucose utilization, and to determine the role of endogenous GH in altered metabolic states such as diabetes mellitus and fasting.